CELLULAR AND MOLECULAR IMPACT OF THE MELANOCORTIN RECEPTOR AGONIST PL8177 IN DEXTRAN SODIUM SULFATE (DSS)-INDUCED COLITIS IN RATS
| العنوان: | CELLULAR AND MOLECULAR IMPACT OF THE MELANOCORTIN RECEPTOR AGONIST PL8177 IN DEXTRAN SODIUM SULFATE (DSS)-INDUCED COLITIS IN RATS |
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| المؤلفون: | Priyanka Dhingra, Alison Obr, Carl Spana, John Dodd, Paul Kayne |
| المصدر: | Inflammatory Bowel Diseases. 28:S3-S3 |
| بيانات النشر: | Oxford University Press (OUP), 2022. |
| سنة النشر: | 2022 |
| مصطلحات موضوعية: | Hepatology, Gastroenterology, Immunology and Allergy |
| الوصف: | INTRODUCTION The melanocortin 1 receptor (MC1r)–specific agonist PL8177 and its main metabolite PL8435 have demonstrated MC1r binding affinity and functional activity that mirrors that of α-melanocyte stimulating hormone (a-MSH). a-MSH has been demonstrated to be effective in reducing inflammation in numerous experimental models. This study investigates the effects of PL8177 on inflammation, cell population composition, and gene and protein expression in colons from a DSS–induced rat model of colitis. The objective is to determine the effectiveness of PL8177 in this model and to characterize its underlying mechanism of action. METHODS Male Wistar rats received 5% DSS in drinking water for 3 days to induce colitis. Rats in the sham group received drinking water only (each group n=6). The other groups received vehicle control (placebo)–filled capsules; PL8177-filled capsules at 20, 50, and 100 μg/animal (by oral gavage); or oral mesalazine (positive control). At termination on day 8, 24 hours after the last dosing, colon tissues were harvested, dissected and snap frozen with liquid nitrogen. Colon samples were analyzed for cytokine levels, single nuclei RNA-seq, and data-independent acquisition tandem mass spectrometry (LC/MS DIA). Colitis was assessed by a disease activity index (diarrhea and rectal bleeding), colon length shortening, colon weight gain, and histopathological assessment. The total colitis index, was used to assess inflammatory damage. RESULTS Colitis was induced in rats treated with DSS. Oral PL8177 50 μg/animal treatment showed a significant improvement in colon weight (53% reduction), stool consistency, and fecal occult blood score compared to vehicle. There was a significant (P CONCLUSION Oral PL8177 treatment of inflamed colon showed significant improvement in markers of colitis in the rat model compared to the placebo and mesalazine control groups supporting the aim of treating inflammatory bowel disease in humans. Genomic and proteomic data will be interpreted in the context of disease change to identify alterations in immune and cellular states of the experimental colons. |
| تدمد: | 1536-4844 1078-0998 |
| DOI: | 10.1093/ibd/izac015.005 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::958fc3ff53d1b44cdbedd740dd8cfcfe https://doi.org/10.1093/ibd/izac015.005 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....958fc3ff53d1b44cdbedd740dd8cfcfe |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15364844 10780998 |
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| DOI: | 10.1093/ibd/izac015.005 |